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Comic style panels explain how epidemic organ failures devastated mankind in the future ("Depraved Heart Murder at Sanitarium Square"). The multi-billion dollar biotech company GeneCo emerged as a result. It provided for-profit organ transplantation, in addition to financing options. GeneCo was able to even repossess defaulted organs. Clients who were behind on payments feared the "organ repo men", contracted by GeneCo to recover GeneCo's property by any means necessary.
The president of GeneCo, Rotti Largo, is dying. Meanwhile, Shilo Wallace, a 17 year-old, believes she inherited a rare blood disease from her deceased mother. She visits her mother's mausoleum ("Things You See in a Graveyard (Part One)") and runs into GraveRobber, who is digging up bodies. They flee from GenCops and enter a massive graveyard ("21st Century Cure"). After passing out, Shilo wakes up ("Shilo Wakes") to find her overprotective father, Nathan Wallace, watching her. He has kept her locked for 17 years, supposedly because of her disease. Shilo is bitter towards her mother, Marni (Sarah Power), for giving her the genetic disease ("Infected"). Nathan prepares for work as the head Repo Man for GeneCo ("Legal Assassin"). Previously a surgeon, Nathan was forced by Rotti into becoming a Repo Man. Marni had left Rotti for Nathan, so Rotti killed Marni and convinced Nathan that he was responsible for her death. Rotti promised to keep it secret if Nathan went to work for GeneCo.
Rotti's children, Luigi, Pavi, and Carmelo Largo/Amber Sweet, meet at a GeneCo warehouse. Luigi and Pavi bicker over who will inherit GeneCo ("Mark It Up"). Nathan, meanwhile, repossesses an intestine ("Thankless Job"). The two siblings irritate Blind Mag, a famous pop-opera singer who works for GeneCo. Amber joins in and taunts Mag about being her replacement. Rotti then introduces Mag to Shilo, who Mag thought had died at birth.
Nathan, while repossessing a spine, calls Shilo, who is under guard by Rotti's henchgirls ("Inopportune Telephone Call"). GraveRobber then helps Shilo escape ("GraveRobber and Shilo Escape"). Rotti announces that Blind Mag will be performing her final song. GraveRobber explains Zydrate, which is harvested from the brains of corpses. Those who are addicted to surgery, including Amber, need Zydrate to ease the pain. Amber arrives and gets a shot of the drug, explaining that she will be replacing Blind Mag after Mag's eyes are repossessed after her final song ("Zydrate Anatomy"). GenCops arrive and everyone scrambles to escape, except for Amber and her two valets, who hold her up as she passes out. Nathan delivers the repossessed spine to Rotti, who gives Nathan his next target: Blind Mag. However, Nathan refuses. Rotti, Pavi, and Luigi follow Nathan as he kills another victim, trying to guilt Nathan into repossessing Blind Mag's eyes ("Night Surgeon").
Later, Rotti sends his henchgirls with Blind Mag to Shilo's house. Blind Mag reveals that she is Shilo's godmother, and that she and Marni were good friends, prior to Marni's death. Blind Mag tries to convince Shilo to come to the Genetic Opera, while also warning Shilo to be careful with GeneCo ("Chase the Morning"). Nathan arrives and kicks Blind Mag out ("Come Back!"). After Shilo says that Repo Men will take Blind Mag's eyes, Nathan insists there are no such people. When she resists, he asks what a 17 year old could possibly do ("What Chance Has a 17 Year Old Girl?").
Back at GeneCo, Amber complains to Rotti that her latest surgery ruined her face. Rotti told her not to get so many surgeries, but he eventually says that he will take care of it ("Happiness is Not a Warm Scalpel"). After she leaves, Rotti signs his will, which shows Shilo as his sole benefactor. Nathan finds the GenCops searching his basement. They are there to find the "rogue Repo Man". Nathan finds Shilo left and the GenCops stole Marni's body ("Tonight We Are Betrayed").
Everyone arrives at the Opera, where the performance begins ("We Started This Op'ra Shit!"). Amber takes the stage for her premier, but her solo is cut short when she trips and her face falls off ("Blame Not My Cheeks"). Mag sings her final song, ending it by gouging out her eyes, stating that she'd rather be blind ("Chromaggia"). Rotti cuts the cords suspending Mag, dropping and impaling her on a fence ("Mag's Fall"). Rotti insists that Mag's death is part of the performance and convinces the audience to stay by saying that he will cure Shilo's illness ("Pièce De Résistance").
Shilo attacks Nathan in his Repo Man gear, hitting him in the head with a shovel. She then realizes that the Repo Man is her father ("Let the Monster Rise"). Rotti then reveals that Nathan has been making Shilo sick by giving her poison ("The Man Who Made You Sick"). Nathan explains that he was trying to protect her from the terrible world. Rotti tells Shilo that if she kills her father, she will inherit GeneCo ("Cut the Ties"). When she refuses, Rotti uses the last of his strength to shoot Nathan ("Shilo Turns Against Rotti"). Rotti then dies on-stage from his disease. Shilo and Nathan say goodbye before Nathan dies ("I Didn't Know I'd Love You So Much"). Shilo leaves, free from her genetic destiny ("Genetic Emancipation").
The following day, GraveRobber reads about Shilo turning down the GeneCo inheritance ("Epitaph"). Amber takes control of GeneCo and auctions off the face that fell off to Pavi.
- Raven as Shilo Wallace
- Dr. Facilier as Rotti Largo
- Moon Knight as Nathan Wallace
- Shura as Blind Mag
- Rosette Christopher as Amber Sweet
- Sephiroth as Luigi Largo
- Kuja as Pavi Largo
- Red X as GraveRobber
Repo! The Genetic Opera holds the record for the most songs ever composed into one film, with a total of 64. This is the official list of all the songs in the film. Some have been cut from the film (e.g. "Come Up and Try My New Parts", "Can't Get It Up if the Girl's Breathing", and "Needle Through a Bug.").
Joan Jett appears as a guitarist in "Seventeen", and Melora Creager of Rasputina plays cello on the soundtrack. A 7-track demo CD, dubbed the "Pre-Surgery Sampler", was released on July 24, 2008. A 22-track soundtrack was released on September 30. Songs do not appear in the same sequence on the CD as they do in the film. On February 20, 2009, an extended edition of the soundtrack was released online. The "Deluxe Edition" contains 38 tracks, and the song "Zydrate Anatomy" was re-cut and used in its film version for this edition.
In the film, the following songs are performed: (* = instrumental)
- "Depraved Heart Murder at Sanitarium Square"*
- "Genetic Repo Man" - GraveRobber and chorus
- "The Prognosis"*
- "Things You See in a Graveyard (Part 1)" - Rotti and Mourners
- "21st Century Cure" - GraveRobber, Gentern on air-raid siren, and Shilo (Shilo's part is only in the film)
- "Shilo Wakes" - Nathan and Shilo
- "Infected" - Shilo
- "Nathan's Story"*
- "Legal Assassin" - Nathan, Marni, and Ghostly whispers
- "Lungs and Livers" - GeneCo Chorus
- "Mark It Up" - Genterns, Amber, Luigi, and Pavi
- "Tao of Mag (Part 1)" - Mag and Chinese chorus
- "Rotti's Story"*
- "Things You See in a Graveyard (Part 2)" -Rotti
- "Limo Ride" - Rotti and Shilo
- "Thankless Job" - Nathan and Repo victim
- "A Ventriloquist's Mess"*
- "Tao of Mag (Part 2)" - Mag and Chinese chorus
- "No Organs? No Problemo!" - GeneCo chorus
- "Largo's Little Helpers" - Child chorus
- "Genterns" - Genterns and Pavi
- "Luigi, Pavi, Amber Harass Mag" - Luigi, Fair patron, Gofers, Mag, Amber, Pavi, and Rotti
- "Seeing You Stirs Memories (Part 1)" - Rotti
- "Blind Mag's Story"*
- "Seeing You Stirs Memories (Part 2)" - Rotti and Mag
- "My, What Big Scissors You Have" - Announcers and Shilo
- "Housecall" - Rotti (spoken)
- "Inopportune Telephone Call" - Nathan and Shilo
- "Before the Escape"*
- "GraveRobber and Shilo Escape" - GraveRobber and Shilo
- "Zydrate Support Network" - News reporter and Rotti
- "Worthy Heirs?"*
- "Zydrate Anatomy" - Zydrate addicts, GraveRobber, Shilo, Amber, and Genterns
- "Disposal Crew" - Disposal crew
- "A Dump Truck Home"*
- "Who Ordered Pizza?" - Luigi, Pavi, Nathan, Rotti, and Amber
- "Night Surgeon" - Nathan, Rotti, Henchgirls, Luigi, Pavi, and Genterns
- "The Visitor"*
- "Chase the Morning" - Mag, Shilo, and Marni
- "Everyone's a Composer" - Mag, Nathan, and Shilo
- "Come Back!" - Nathan and Shilo
- "What Chance Has a 17 Year Old Girl" - Nathan and Shilo
- "Seventeen" - Shilo and Chorus
- "Happiness is Not a Warm Scalpel" - Amber and Rotti
- "Gold" - Rotti
- "Nathan Discovers Rotti's Plan" - Nathan and Shilo
- "Tonight We Are Betrayed" - Nathan
- "At the Opera Tonight" - Shilo, Mag, Nathan, Amber, GraveRobber, Rotti, Luigi, Pavi, and chorus
- "Bloodbath!" - GraveRobber
- "Not Your Parents' Opera"*
- "We Started This Op'ra Shit!" - Band leader, Genterns, Luigi, Pavi, Single mother, Rotti, Opera audience, and GeneCo chorus
- "Interrogation Room Challenge" - Rotti
- "Blame Not My Cheeks" - Announcer, Amber, Eunuch valets, and GeneCo chorus
- "Chromaggia" - Mag
- "Mag's Fall"*
- "Pièce De Résistance" - Rotti
- "Let the Monster Rise" - Nathan and Shilo
- "A Ten Second Opera"*
- "Sawman's Lament" - Rotti, Luigi, Pavi, Shilo, Nathan, and Opera audience
- "The Man Who Made You Sick" - Rotti, Shilo, and Nathan (connected with "Sawman's Lament")
- "Cut the Ties" - Rotti, Luigi, Shilo, and Pavi
- "Shilo Turns Against Rotti" - Shilo, Rotti, and Nathan (connected to "Cut the Ties")
- "The King is Dead" - Rotti (spoken)
- "I Didn't Know I'd Love You So Much" - Shilo and Nathan
- "Genetic Emancipation" - Shilo and chorus
- "Epitaph" - GraveRobber and Zydrate addicts
- "VUK-R" - Katie Fitzgerald (end credits)
- "Repo Man" - Pavi (end credits)
- "Needle Through a Bug" - GraveRobber, Shilo, and Chorus (deleted scene, end credits)
- "Bravi!" - Mag, Luigi, Pavi, Rotti, Amber, and Genterns (deleted scene, end credits)
- "Aching Hour" - Mag (end credits)
Bits and pieces of some of these songs were used in the film. Most of the songs' scenes were entirely cut (*).
- "Crucifixus" - Mag and Ghostly Whispers (used as the screen closes in to GeneCo; instrumental version used in film)
- "Bravi!"* - Mag, Pavi, Luigi, Rotti, and Amber (end credits, a commercial that would have been used before "Mark It Up"; heard briefly between "Infected" and Nathan's Story)
- "Tao of Mag" - Mag (a commercial starring Mag that promotes the Genetic Opera; heard briefly between "Mark It Up" and Rotti's Story)
- "Can't Get It Up if the Girl's Breathing?"* - Amber, Eunuch valets, and GraveRobber (Amber telling GraveRobber that there are other ways to pay for Zydrate; would have succeeded "Housecall")
- "Come Up and Try My New Parts"* - Amber (Amber's attempt to seduce GraveRobber to get out of paying for Zydrate; comes after "Can't Get It Up")
- "GraveRobber and Shilo Escape" - GraveRobber, Shilo, and Amber (GraveRobber and Shilo escape from the Italian festival; alternate version used in film, Amber not included)
- "Buon Giorno"* - Rotti, Pavi, Luigi, and Genterns (Genetic Opera greeting; would have come after "We Started This Op'ra Shit!")
- "Rotti's Chapel Sermon"* - Rotti (the scene was reedited to make up "Interrogation Room Challenge"; succeeds "Buon Giorno")
- "Needle Through a Bug"* - GraveRobber, Shilo, and Chorus (deleted scene where Shilo must pass another of Rotti's tests; succeeded "Rotti's Chapel Sermon") and plays entirely during credits
- "Aching Hour"* - Blind Mag (Mag sings about her imminent death during the Renaissance festival; plays entirely during credits)